The oxygen supply of the retina is provided by both the choroidal and retinal circulation. Because of the high oxygen needs of the retina, any alteration in circulation such as seen in diabetic retinopathy, hypertension, sickle cell anemia, and vascular diseases can result in impairment. Pathological conditions in the retina and optic nerve head (ONH) can cause vision loss and blindness. Both structures have a high demand for oxygen, and loss of the normal oxygen supply through vascular insufficiency is believed to play an important role in retinal and ONH pathology. See, G. A. Cioffi et al., “Optic nerve blood flow in glaucoma,” Semin. Ophthalmol., Vol. 14, no. 3, pp. 164-170 (1999); A. Harris et al., “Simultaneous management of blood flow and IOP in glaucoma,” Acta Ophthalmol. Scand., Vol. 79, pp. 336-341 (2001); and S. S. Hayreh, “Factors influencing blood flow in the optic nerve head,” J. Glaucoma, Vol. 6, pp. 412-425 (1997). Hypoxia of the retina and ONH is believed to be a factor in the development of ocular vascular disorders such as diabetic retinopathy, arterial venous occlusion disease, and glaucoma. See, K. R. Denninghoff et al., “Retinal imaging techniques in diabetes,” Diabetes Technol. Ther., Vol. 2, pp. 111-113 (2000); E. Stefansson et al., “Oxygenation and vasodilation in relation to diabetic and other proliferative retinopathies,” Ophthalmic Surg., Vol. 14, pp. 209-226 (1983); A. Yoneya et al., “Retinal oxygen saturation levels in patients with central retinal vein occlusion,” Ophthalmology, Vol. 109, pp. 1521-1526 (2002); and E. Stefansson et al., “Optic nerve oxygen tension in pigs and the effect of carbonic anhydrase inhibitors,” Invest Opthalmol. Vis. Sci., Vol. 40, pp. 2756-2762 (1999). The ability to obtain relative measurements of oxygen saturation in the human ocular fundus could aid diagnosis and monitoring of these and other disorders. For example, measurement of changes in retinal and ONH oxygen saturation under controlled conditions could establish relationships between oxygen consumption, blood sugar levels, and vascular autoregulatory function in diabetic retinopathy. Assessment of oxygenation in the ONH may facilitate early detection of the onset of glaucoma, a disease in which timely diagnosis is crucial for effective treatment.
Measurements of oxygen tension (pO2) in the ONH have been performed using O2-sensitive microelectrodes inserted into the eye. See, e.g., E. Stefansson et al., “Optic nerve oxygen tension in pigs and the effect of carbonic anhydrase inhibitors,” Invest. Ophthalmol. Vis. Sci., Vol. 40, pp. 2756-2762 (1999). Although this technique is accurate and can determine pO2 distribution in three dimensions, its invasive nature limits its use to animal models and precludes clinical applications. Another technique involving injection of a phosphorescent dye has been used to study pO2 in the retinal and choroidal vessels, as well as the microvasculature of the ONH rim. See, e.g., S. Blumenroder et al., “The influence of intraocular pressure and systemic oxygen tension on the intravascular pO2 of the pig retina as measured with phosphorescence imaging,” Surv. Opthalmol., Vol. 42, pp. S118-S126 (1997). However, use of the dye in humans has yet to be approved.
Imaging techniques based on spectral changes of oxygenated hemoglobin (HbO2) and reduced hemoglobin (Hb) have been employed in humans to assess oxygen saturation in the ocular fundus, and in retinal artery/vein pairs. See Yoneya et al., (2002); and J. M. Beach et al., “Oximetry of retinal vessels by dual-wavelength imaging: calibration and influence of pigmentation,” J. Appl. Physiol., Vol. 86, pp. 748-758 (1999). These methods have been based most often on recordings at several discrete wavelengths chosen for their relative sensitivity to changes in oxygen saturation. See, M. Crittin et al., “Hemoglobin oxygen saturation (So2) in the human ocular fundus measured by reflectance oximetry: preliminary data in retinal veins,” Klin. Monatsbl. Augeniheilkd, Vol. 291, pp. 289-291 (2002); F. C. Delori, “Noninvasive technique for oximetry of blood in retinal vessels,” Appl. Optics, Vol. 27, pp. 1113-1125 (1998); J. B. Hickam et al., “A study of retinal venous blood oxygen saturation in human subjects by photographic means,” Circulation, Vol. 27, pp. 375-383 (1963); J. Hickam et al., “Studies of the retinal circulation in man: observations on vessel diameter, arteriovenous oxygen difference, and mean circulation time,” Circulation, Vol. 33, pp. 302-316 (1966); and J. S. Tiedeman et al., “Retinal oxygen consumption during hyperglycemia in patients with diabetes without retinopathy,” Opthalmology, Vol. 105, pp. 31-36 (1998).
Full spectral methods, employing a continuous range of wavelengths, have been used to record the reflectance profile versus wavelength from the ocular fundus. See, F. C. Delori, “Reflectometry measurements of the optic disc blood volume,” in Ocular Blood Flow in Glaucoma Means, Methods and Measurements, G. N. Lambrou, E. L. Greve eds., Berkely, Calif., Kugler and Ghedini, pp. 155-163 (1989); and F. C. Delori et al., “Spectral reflectance of the human ocular fundus,” Appl. Optics, Vol. 28, pp. 1061-1077 (1989). Full spectral imaging technique has also been employed to measure oxygen saturation in retinal arteries and veins under various conditions. See D. Schweitzer et al., “In vivo measurement of the oxygen saturation of retinal vessels in healthy volunteers,” IEEE Trans Biomed Eng., Vol. 46, pp. 1454-1465 (1999); and D. Schweitzer et al., “A new method for the measurement of oxygen saturation at the human ocular fundus,” Int. Ophthalmol., Vol. 23, pp. 347-353. (2001). Oxygen saturation in the ocular fundus has been mapped using Fourier transform spectral imaging. See, Yoneya et al., (2002). The full spectral technique employed most often uses a high resolution imaging spectrograph to collect the spectral information from a band of tissue in a single spatial dimension. The method acquires data rapidly and is applicable for use in human subjects. See Schweitzer et al., (1999); and Schweitzer et al., (2001).